Structure-based design of immunologically active therapeutic peptides.
Peptides are flexible molecules and can adopt local structural features of protein, such as secondary structure, hydrophobicity, and distribution of electrostatic charges, and so forth, and mimic their functions. Therapeutic peptidomimetics that are immunologically relevant are developed by engineering the surface loop structures in the proteins and receptors. The class of molecules targeted include immunoglobulin fold-containing molecules: antibody, cell-surface CD4 receptors and cystine-knot-containing receptor family members: tumor necrosis factor (TNF), CD40, and p185/Neu receptors. We have used the loops involved in the molecular recognition as a template and developed peptidomimetics that interfere with the functions of the target molecules. In this article, two molecular targets are discussed: (1) immunoglobulin fold-containing CD4 receptor and (2) cystine-knot-containing TNF receptor (TNFR).
Murali
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Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104-6082, USA. murali@xray.med.upenn.edu
Greene
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MI
D000818:Animals; D015704:CD4 Antigens / Q000737:chemistry / Q000276:immunology; D015195:Drug Design; D006801:Humans; D007167:Immunotherapy; D010455:Peptides / Q000737:chemistry / Q000276:immunology* / Q000627:therapeutic use; D017510:Protein Folding; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000276:immunology; D013329:Structure-Activity Relationship
D015704:CD4 Antigens; D010455:Peptides; D018124:Receptors, Tumor Necrosis Factor